Alcoholic injury mitigating agent

ABSTRACT

The present invention relates to an alcoholic injury mitigating agent comprising krill oil as an active ingredient. The krill oil preferably comprises phospholipids in an amount of at least 30% by weight, ω3 polyunsaturated fatty acids in an amount of at least 5% by weight of the total fatty acids, eicosapentaenoic acid in an amount of at least 2% by weight of the total fatty acids, or docosahexaenoic acid in an amount of at least 1% by weight of the total fatty acids.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation application of U.S. patentapplication Ser. No. 13/820,170, filed on Mar. 1, 2013, the entirecontents of which are incorporated herein by reference and priority towhich is hereby claimed. Application Ser. No. 13/820,170 is the U.S.National stage of application No. PCT/JP2011/069876, filed Sep. 1, 2011.Priority under 35 U.S.C. §119(a) and 35 U.S.C. §365(b) is hereby claimedfrom Japanese Application No. 2010-195730, filed Sep. 1, 2010, thedisclosure of which is also incorporated herein by reference.

TECHNICAL FIELD

The present invention relates to agents for mitigating injuries causedby alcohol consumption such as drunken sickness and hangover, andinjuries to the liver, blood, blood sugar and the like, as well asalcohol metabolism promoting agents.

BACKGROUND ART

Alcoholic beverages such as beer, wine, whiskey, rice wine and shochuhave been enjoyed by people since long ago. A wide variety of alcoholicbeverages have actually been produced and sold, contributing to people'srich dietary life.

While having such an aspect of enjoying people, alcoholic beverages mayproduce undesirable symptoms. Excessive drinking may cause drunkensickness or hangover where the symptoms of drunkenness (such asheadache, dizziness, nausea, dehydration) persist on and/or after thefollowing day of drinking. Further, excessive drinking for a long timemay develop symptoms such as gout and liver dysfunction. Suchalcohol-induced symptoms are common in that they are attributed to anincrease in blood alcohol concentration caused by drinking.

There are several known inventions intended for promotion of alcoholicmetabolism after drinking. For example, Japanese Unexamined PatentApplication Publication No. 11-276116 discloses an alcohol metabolismpromoting agent comprising a processed pork product prepared from porktreated with a protease (Patent Document 1). Japanese Unexamined PatentApplication Publication No. 2002-161045 discloses an alcohol metabolismameliorant comprising a fermented rice bran and soybean extract (PatentDocument 2). Japanese Unexamined Patent Application Publication No.2001-226277 discloses an alcohol absorption and metabolism regulatingagent comprising a processed soybean product as an active ingredient(Patent Document 3).

CITATION LIST Patent Documents

-   [Patent Document 1] Japanese Unexamined Patent Application    Publication No. 11-276116-   [Patent Document 2] Japanese Unexamined Patent Application    Publication No. 2002-161045-   [Patent Document 3] Japanese Unexamined Patent Application    Publication No. 2001-226277

SUMMARY OF INVENTION Technical Problem

An object of the present invention is to provide a pharmaceuticalpreparation, supplement, food, and the like that can mitigate injuriescaused by alcohol consumption such as drunken sickness and hangover, andinjuries to the liver, blood, blood sugar and the like, or an alcoholmetabolism promoting agent, each of which comprises safe ingredients inan easy-to-consume form.

Solution to Problem

In the process of studying krill oil, the present inventors have foundthat krill oil has unexpected effects on alcohol metabolism, andcompleted the present invention.

The present invention provides the following alcoholic injury mitigatingagent, and the following food and beverage comprising the same:

(1) An alcoholic injury mitigating agent comprising krill oil as anactive ingredient;

(2) The alcoholic injury mitigating agent according to (1), wherein themitigation of alcoholic injury is suppression of an increase in bloodethanol concentration, mitigation of a symptom of drunkenness, promotionof recovery from the symptoms of drunkenness, suppression of liverinjury, suppression of dehydration, or suppression of an increase inblood glucose level;

(3) The alcoholic injury mitigating agent according to (1) or (2),wherein the mitigation of alcoholic injury is based on suppression ofalcohol absorption and/or promotion of alcohol metabolism, each inducedby the krill oil;

(4) The alcoholic injury mitigating agent according to any one of (1) to(3), wherein the krill oil comprises phospholipids in an amount of atleast 25% by weight;

(5) The alcoholic injury mitigating agent according to any one of (1) to(4), wherein at least 5% by weight of the total fatty acids in the krilloil is ω3 polyunsaturated fatty acids;

(6) The alcoholic injury mitigating agent according to any one of (1) to(5), wherein at least 2% by weight of the total fatty acids in the krilloil is eicosapentaenoic acid;

(7) The alcoholic injury mitigating agent according to any one of (1) to(6), wherein at least 1% by weight of the total fatty acids in the krilloil is docosahexaenoic acid;

(8) The alcoholic injury mitigating agent according to any one of (1) to(7), wherein the daily consumption amount of the krill oil is in therange of 1 to 20000 mg;

(9) A food and beverage for ingesting the alcoholic injury mitigatingagent according to any one of (1) to (8); and

(10) The food and beverage according to (9), wherein the krill oil isingested in an amount of 1-20000 mg per a single dose.

In another aspect, the present invention provides, but is not limitedto, the alcohol metabolism promoting agent as set forth below in (11) to(16):

(11) An alcohol metabolism promoting agent comprising krill oil;

(12) The alcohol metabolism promoting agent according to (11), whereinthe krill oil is extracted from a krill-derived starting material usingan organic solvent;

(13) The alcohol metabolism promoting agent according to (11) or (12),wherein the krill oil is extracted from a krill-derived startingmaterial using ethanol;

(14) The alcohol metabolism promoting agent according to any one of (11)to (13), wherein the krill oil comprises phospholipids in an amount ofat least 25% by weight;

(15) The alcohol metabolism promoting agent according to any one of (11)to (14), wherein ω3 polyunsaturated fatty acids accounts for at least 5%by weight of the total fatty acids in the krill oil; and

(16) The alcohol metabolism promoting agent according to any one of (11)to (15), wherein the krill oil contains astaxanthin in an amount of atleast 100 ppm.

Further, the present invention provides the following methods:

A method for promoting alcohol metabolism, comprising administering analcohol metabolism promoting agent comprising krill oil; and

A method for preventing or ameliorating alcoholic liver injury, tissueinjury associated with dehydration, or a disease caused by an increasein blood glucose level, the method comprising administering an alcoholmetabolism promoting agent comprising krill oil.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 shows the schedule of the administrations of the test substanceand alcohol performed in Example 1. Rats were used as test animals and a60% (v/v) ethanol solution was administered as alcohol.

FIG. 2 shows the changes in blood ethanol concentration in the ratsaccording to Example 2. □: Untreated group (A1), ●: 60% (v/v)ethanol+olive oil group (A2), Δ: 60% (v/v) ethanol+krill oil (200 mg/kg)group (A3), and ▴: 60% (v/v) ethanol+krill oil (1,000 mg/kg) group (A4).The data in the figure are expressed as averages. $$ represents p<0.01,vs. untreated group (Aspin-Welch test); ** represents p<0.01, vs.ethanol+olive oil group (Aspin-Welch test); # represents p<0.05, vs.ethanol+olive oil group (Student-t test); and ## represents p<0.01, vs.ethanol+olive oil group (Student-t test).

FIG. 3 shows the results of observation of general condition in the ratsafter ethanol administration in Example 2. The general condition score,which is based on walking state and righting reflex, reflects the stateof drunkenness. □: Untreated group (A1), ●: 60% (v/v) ethanol+olive oilgroup (A2), Δ: 60% (v/v) ethanol+krill oil (200 mg/kg) group (A3), and▴: 60% (v/v) ethanol+krill oil (1,000 mg/kg) group (A4). The data in thefigure are expressed as averages. $$ represents p<0.01, vs. untreatedgroup (Aspin-Welch test); ** represents p<0.01, vs. ethanol+olive oilgroup (Aspin-Welch test); and ## represents p<0.01, vs. ethanol+oliveoil group (Student-t test).

FIG. 4 shows the changes in hematocrit (HCT) according to Example 2. Thebars in the graph show, in the order from left to right, the values forthe untreated group (A1), the 60% (v/v) ethanol+olive oil group (A2),the 60% (v/v) ethanol+krill oil (200 mg/kg) group (A3), and the 60%(v/v) ethanol+krill oil (1,000 mg/kg) group (A4). The data in the figureare expressed as averages. & represents p<0.05, vs. untreated group(Student-t test); && represents p<0.01, vs. untreated group (Student-ttest); ** represents p<0.01, vs. ethanol+olive oil group (Aspin-Welchtest); and ## represents p<0.01, vs. ethanol+olive oil group (Student-ttest).

FIG. 5 shows the changes in blood aspartate aminotransferase (AST)activity (IU/L) in the rats after oral alcohol administration accordingto Example 2. This enzyme activity is found in the liver, so the ASTactivity in the blood serves as an indicator of liver injury. The barsin the graph show, in the order from left to right, the values for theuntreated group (A1), the 60% (v/v) ethanol+olive oil group (A2), the60% (v/v) ethanol+krill oil (200 mg/kg) group (A3), and the 60% (v/v)ethanol+krill oil (1,000 mg/kg) group (A4). The data in the figure areexpressed as averages. $$ represents p<0.01, vs. untreated group (Aspin-Welch test); and # represents p<0.05, vs. ethanol+olive oil group(Student-t test).

FIG. 6 shows the changes in blood alanine aminotransferase (ALT)activity (IU/L) in the rats after oral alcohol administration accordingto Example 2. This enzyme is found in the liver, so the ALT activity inthe blood serves as an indicator of liver injury. The bars in the graphshow, in the order from left to right, the values for the untreatedgroup (A1), the 60% (v/v) ethanol+olive oil group (A2), the 60% (v/v)ethanol+krill oil (200 mg/kg) group (A3), and the 60% (v/v)ethanol+krill oil (1,000 mg/kg) group (A4). The data in the figure areexpressed as averages. $ represents p<0.05, vs. untreated group (Aspin-Welch test); and # represents p<0.05, vs. ethanol+olive oil group(Student-t test).

FIG. 7 shows the changes in blood glucose level in the rats according toExample 2. The bars in the graph show, in the order from left to right,the values for the untreated group (A1), the 60% (v/v) ethanol+olive oilgroup (A2), the 60% (v/v) ethanol+krill oil (200 mg/kg) group (A3), andthe 60% (v/v) ethanol+krill oil (1,000 mg/kg) group (A4). The data inthe figure are expressed as averages. $$ represents p<0.01, vs.untreated group (Asp in-Welch test); ** represents p<0.01, vs.ethanol+olive oil group (Aspin-Welch test); and # represents p<0.05, vs.ethanol+olive oil group (Student-t test).

FIG. 8 shows the changes with time in breath ethanol concentrationaccording to Example 3. The horizontal axis represents time afteralcohol consumption (in min). ●: Krill oil consumption, and ◯: Olive oilconsumption. The data in the figure are expressed as the averages(Mean±SE) of the ethanol concentrations in the breath samples from 5subjects. * represents p=0.04, vs. olive oil (Wilcoxon signed ranktest).

FIG. 9 shows the changes with time in breath acetaldehyde concentrationaccording to Example 3. The horizontal axis represents time afteralcohol consumption (in min). Solid line: Krill oil consumption, anddotted line: Olive oil consumption.

FIG. 10 shows the changes with time in breath acetaldehyde concentrationaccording to Example 4 along with the results obtained in Example 3. Thehorizontal axis represents time after alcohol consumption (in min) ♦:Krill oil consumption, ▪: Olive oil consumption, ▴: Refined fish oilconsumption, and ×: Soybean lecithin consumption.

DESCRIPTION OF EMBODIMENTS

The present invention will be more specifically described below.

As used herein, “krill” may be any arthropod that belongs to, subclassMalacostraca, class Crustacea, phylum Arthropoda, and includesarthropods that belong to order Euphausiacea, superorder Eucarida,subclass Malacostraca, class Crustacea, phylum Arthropoda, such asAntarctic krill (Euphausia superba), and arthropods that belong to orderMysida, superorder Peracarida, subclass Malacostraca, class Crustacea,phylum Arthropoda, such as mysids caught in the oceans near Japan.

As used herein, “krill oil” refers to the oil obtained from the krilldescribed above.

The krill oil is characterized in that it has high phospholipidscontent. Phospholipid is known as a major constituent of the cellmembrane and refers to a substance that has a hydrophilic phosphatemoiety and a hydrophobic fatty acid moiety. Phospholipids are dividedinto glycerophospholipids and sphingophospholipids by the difference intheir skeletal structure. As referred to herein, phospholipids includeboth types of phospholipids, with glycerophospholipids being preferred.Glycerophospholipids include, but are not limited to, phosphatidylcholine, phosphatidyl ethanolamine, phosphatidyl serine,phosphatidylinositol, phosphatidylglycerol, cardiolipin, andphosphatidic acid, and mixtures of two or more thereof. In the presentinvention, at least phosphatidyl choline is preferably contained asphospholipids. The phospholipids content in the krill oil is, forexample, 5-80% by weight and particularly preferably 30-60% by weight.Alternatively, the krill oil can contain phospholipids in an amount ofpreferably at least 25% by weight and more preferably at least 35% byweight.

The krill oil is also characterized in that it contains ω3polyunsaturated fatty acids. As used herein, “ω3 polyunsaturated fattyacids” means fatty acids having 18 or more carbons and 3 or more doublebonds or preferably 5 or more double bonds, in which the third andfourth carbons from the terminal carbon opposite to the carboxyl side ofthe fatty acid molecule are joined by a double bond. Such fatty acidsinclude, but are not limited to, α-linolenic acid (18:3),eicosapentaenoic acid (20:5), docosapentaenoic acid (22:5), anddocosahexaenoic acid (22:6). ω3 polyunsaturated fatty acids may bepresent in a free state or in the form of lipids involving ester bonds.The proportion of ω3 polyunsaturated fatty acids in the total fattyacids present in the krill oil is, for example, 5-60% by weight,preferably 10-50% by weight and more preferably 10-30% by weight. It ispreferred for the purpose of the present invention that the proportionof ω3 polyunsaturated fatty acids in the total fatty acids be containedin an amount of at least 5% by weight, more preferably at least 10% byweight and still more preferably at least 15% by weight. It isparticularly preferred that eicosapentaenoic acid be contained in anamount of at least 2% by weight and preferably at least 10% by weight,and/or that docosahexaenoic acid be contained in an amount of at least1% by weight and preferably at least 3% by weight.

The krill oil may further contain astaxanthin. Astaxanthin, a compoundthat belongs to the carotenoid family, is generally found in shellfishsuch as crab and shrimp. Astaxanthin may be present in a free state orin the form of lipids involving ester bonds, and is contained in thekrill oil in an amount of, for example, 20-1,000 ppm, preferably 50-600ppm, more preferably 50-500 ppm, still more preferably 100-400 ppm, andparticularly preferably 100-250 ppm.

As long as having the above-mentioned properties, the krill oil used inthe present invention may be prepared by any methods—for example, it canbe prepared with reference to known methods as typically disclosed in WO2010/035749 A1 and WO 2010/035750 A1. The krill oil can be obtained by,for example, extracting it from solids as a krill-derived startingmaterial using a suitable organic solvent. The suitable organic solventis one or a combination of two or more of, for example, alcohols such asmethanol, ethanol, propanol, isopropanol, butanol, propyleneglycol andbutylene glycol; methyl acetate, ethyl acetate, acetone, chloroform,toluene, pentane, hexane, and cyclohexane, with ethanol or ahexane-ethanol mixture being preferred. In the process of extraction,the solvent mixing ratio or the starting material/solvent ratio may bedesigned as desired.

The foregoing solids as a krill-derived starting material can beobtained by, for example, squeezing the whole or a part of the krill togive a squeezed liquid and heating the resulting squeezed liquid toseparate solids and water-soluble components. Instead of obtaining thesqueezed liquid, the whole or a part of the krill may be directlysubjected to heat coagulation to give solids.

The squeezing can be performed using a commonly used apparatus such as ahydraulic squeezer, a screw press, a meat separator, a press dehydrator,a centrifuge, or a combination thereof.

The squeezed liquid may be heated under atmospheric pressure,pressurized, or reduced pressure conditions at a temperature of 50° C.or higher, preferably 70-150° C. and particularly preferably 85-110° C.The heating is performed to separate solids and water-solublecomponents, and filtration, centrifugation, or other treatments areperformed to give the solids.

The present invention provides an alcoholic injury mitigating agentcomprising krill oil as an active ingredient. The alcoholic injurymitigating agent can be used for mitigating injuries caused by alcoholconsumption, and this effect is based on the alcohol absorptioninhibition action and/or alcohol metabolism promotion action of thekrill oil. Therefore, the present invention also provides an alcoholmetabolism promoting agent comprising krill oil. As referred to herein,the mitigation of alcoholic injury includes, but is limited to,suppression of an increase in blood ethanol concentration, mitigation ofa symptom of drunkenness, promotion of recovery from the symptoms ofdrunkenness, suppression of liver injury, suppression of dehydration, orsuppression of an increase in blood glucose level.

The alcoholic injury mitigating agent and alcohol metabolism promotingagent of the present invention preferably use the krill oil extracted asdescribed above but may use a product containing the krill oil, such asground, shelled, or dried krill.

The alcoholic injury mitigating agent and alcohol metabolism promotingagent comprise an effective amount of the krill oil. As referred toherein, the effective amount may be any amount that is effective eitherfor mitigating injuries caused by alcohol consumption or for promotingalcohol metabolism, for example, such an amount that allows a rat toconsume the krill oil at a concentration of 10-5,000 mg/kg andpreferably 100-2,000 mg/kg daily. The daily effective amount for a humanis preferably 1-5,000 mg/kg and particularly preferably 10-2,000 mg/kg,and more specifically, it is preferred to prepare such a capsule orsupplement that enables consumption of 1-500 mg/kg, preferably 1-200mg/kg and more preferably 1-100 mg/kg daily. Such an amount may beconsumed once daily or in two, three or more divided doses. Asillustrated in Examples, the alcoholic injury mitigating agent andalcohol metabolism promoting agent of the present invention take effecteven if it is consumed 30 minutes before alcohol consumption, andtherefore also preferred are such usages as taking it in an amount of1-20000 mg and preferably 100-5000 mg before alcohol consumption toprevent hangover or the like.

The inventive alcoholic injury mitigating agent and alcohol metabolismpromoting agent comprising krill oil are effective for reducing bloodalcohol concentration and also for reducing the occurrence ofacetaldehyde.

The present invention provides a method for preventing or amelioratingdrunken sickness or hangover, comprising: administering the alcoholicinjury mitigating agent or alcohol metabolism promoting agent comprisingkrill oil to an animal such as a human. Excessive alcohol consumptioncauses symptoms such as headache, nausea, drunkenness, dizziness,malaise, and anorexia. The possible factors associated with thesesymptoms include dehydration caused by alcohol. The alcoholic injurymitigating agent and alcohol metabolism promoting agent of the presentinvention are effective for reducing blood alcohol concentration andtherefore is suitable for the above-mentioned purposes.

The present invention provides a method for preventing or treating asymptom or disease caused by an increase in blood glucose level,comprising: administering the alcoholic injury mitigating agent oralcohol metabolism promoting agent comprising krill oil to an animalsuch as a human. As referred to herein, the symptom caused by anincrease in blood glucose level includes, but is not limited to, malais,thirst, polyuria, hunger sensation, and weight gain. The disease causedby an increase in blood glucose level includes, but is not limited to,complications associated with arteriosclerosis. The alcoholic injurymitigating agent and alcohol metabolism promoting agent of the presentinvention are effective for preventing an increase in blood glucoselevel associated with alcohol consumption and therefore are suitable forthe above-mentioned purposes.

The present invention provides a method for preventing or treatingalcoholic liver injury, comprising: administering the alcoholic injurymitigating agent or alcohol metabolism promoting agent comprising krilloil to an animal such as a human. As referred to herein, the alcoholicliver injury refers to a disease caused by excessive alcohol consumptionfor a long time. The alcoholic liver injury includes, but is not limitedto, chronic hepatitides such as alcoholic fatty liver, alcoholic hepaticfibrosis, and alcoholic cirrhosis, and acute hepatitides such asalcoholic hepatitis.

The alcoholic fatty liver is an early stage of alcoholic liver injury,where decreased liver lipolysis function causes accumulation of neutralfats in the liver, leading to the development of fatty liver. Thealcoholic hepatic fibrosis means a severe alcoholic fatty liver wherenecrosis of hepatocytes and fibrosis of the tissues surrounding thenecrotic area develop. The alcoholic cirrhosis means a severe alcoholichepatic fibrosis where advanced chronic hepatitis causes severedisruption of hepatocytes, bringing the entire liver into the state ofbeing covered with fiber. The alcoholic hepatitis is a disease wherehepatocytes are severely damaged.

Such alcoholic liver injuries are caused by damage to hepatocytes byalcohol. The alcoholic injury mitigating agent and alcohol metabolismpromoting agent of the present invention are capable of protectinghepatocytes and preventing them from being damaged and therefore aresuitable for the above-mentioned purposes.

The mitigation effects for injuries caused by alcohol consumption or thealcohol metabolism promotion effect can be evaluated on the basis of theresults of, for example, (1) blood ethanol concentration, (2)observation of general condition, (3) hematocrit (HCT), (4) bloodaspartate aminotransferase (AST) activity, (5) blood alanineaminotransferase (ALT), (6) blood glucose level, (7) breath ethanolconcentration, and (8) breath acetaldehyde concentration. In the presentspecification, the above-noted parameters were measured by the followingprocedures, unless otherwise specified.

(1) Blood ethanol concentration: This parameter makes it possible toidentify the change in the concentration of alcohol remaining in thebody after alcohol consumption. If alcohol metabolism is promoted, theblood ethanol concentration decreases and recovers faster to its normallevel. The blood ethanol concentration can be measured by ultravioletspectrophotometry using F-Kit Ethanol (J. K. International Inc.).

(2) Observation of general condition: The drunkenness caused by alcoholadministration is evaluated as a score by observing body posture,mobility and righting reflex. If alcohol metabolism is promoted, thedegree of drunkenness is mitigated and the general condition recoversfaster to its normal state. The general condition can be evaluated onthe basis of the following criterion:

0 point: The body posture, mobility and righting reflex are all normal;

1 point: Limbs cannot be kept in balance but walking is possible and therighting reflex is normal (slight drunkenness);

2 points: Limbs cannot be kept in balance and walking is impossible butthe righting reflex is normal (inebriation and somnolence); and

3 points: Limbs cannot be kept in balance, walking is impossible, andthe righting reflex is lost (dead drunkenness and coma).

(3) Hematocrit (HCT): This parameter represents the percentage ofhemocytes in the whole blood. When alcohol is consumed, antidiuretichormone secretion is reduced to thereby promote diuresis, so that thewater content in the body decreases. As a result, the plasma volumedecreases and the amount of hemocytes in the whole blood relativelyincreases, causing an increase in HCT. In other words, the hematocritrepresents the percentage by volume of hemocytes in the blood, and anincrease in this value reflects a decrease in the percentage of water inthe blood. HCT can be used as an indicator of dehydration caused byalcohol consumption. If alcohol metabolism is promoted, dehydration isresolved and thus HCT decreases. HCT can be measured by sheath flow DCdetection using a multi-parameter automated hematology analyzer(XT-2000i, Sysmex Corporation).

(4) Blood aspartate aminotransferase (AST) activity: AST catalyzes thereaction for generating glutamic acid and oxaloacetic acid from asparticacid and 2-oxoglutaric acid. AST is present in hepatocytes, red bloodcells, cardiac muscle, skeletal muscles and elsewhere, and leaks outinto the blood due to necrocytosis or other factors. Therefore,measuring the AST activity in the blood makes it possible to determinethe degree of liver injury induced by alcohol consumption. The ASTactivity can be measured by the JSCC standardization-compliant methodusing an automatic analyzer (Type 7170, Hitachi, Ltd.).

(5) Blood alanine aminotransferase (ALT) activity: ALT catalyzes thereaction for converting pyruvic acid and glutamic acid into alanine andα-ketoglutaric acid. ALT is mainly present in the liver and leaks outinto the blood due to necrosis of hepatocytes or other factors.Therefore, measuring the ALT activity in the blood makes it possible todetermine the degree of livery injury induced by alcohol consumption.The ALT activity can be measured by the JSCC standardization-compliantmethod using an automatic analyzer (Type 7170, Hitachi, Ltd.).

(6) Blood glucose level: Alcohol consumed by drinking or otheractivities is oxidized into acetaldehyde by alcohol dehydrogenase (ADH).This reaction involves reduction of NAD⁺ to NADH and thus produces ashortage of NAD⁺ required in glycolysis, so that glucose degradationthrough glycolysis is inhibited. However, increased NADH concentrationexasperates gluconeogenesis, leading to an increase in blood glucoselevel. Therefore, measuring the blood glucose level makes it possible todetermine the degrees of inhibition of glucose degradation and state ofincreased gluconeogenesis which are caused by alcohol consumption. Theblood glucose level can be measured by the Hexokinase/G6-PDH(hexokinase/glucose-6-phosphate dehydrogenase) method using an automaticanalyzer (Type 7170, Hitachi, Ltd.).

(7) Breath ethanol concentration: The concentration of ethanol containedin breath has a correspondence with the blood ethanol concentration.Therefore, measuring the breath ethanol concentration makes it possibleto identify the change in blood ethanol concentration. The breathethanol concentration can be measured by passing breath through anethanol detector tube (Gastec Corporation, No. 112L) connected to adetector (Gastec Corporation, GV-100S) for about 4 minutes. The tube hasa color change zone, in which the length of the portion of this zonethat changes in color from light red to light blue indicates an ethanolconcentration by a scale on the tube, and resulting value of ethanolconcentration is corrected for the effect of temperature to give ameasured value.

(8) Breath acetaldehyde concentration: Acetaldehyde is a causative agentof uncomfortable feeling and alcoholic liver injury induced by alcoholconsumption. The breath acetaldehyde concentration has a correspondencewith a blood acetaldehyde concentration. Therefore, measuring the breathacetaldehyde concentration makes it possible to identify the change inblood acetaldehyde concentration. The concentration of acetaldehydecontained in breath can be measured by passing breath through an ethanoldetector tube (Gastec Corporation, No. 92L) connected to a detector(Gastec Corporation, GV-100S) for about 2 minutes. The tube has a colorchange zone where the length of the portion of this zone that changes incolor from light red to light blue indicates an ethanol concentration,by a scale on the tube, and resulting value of ethanol concentration iscorrected for the effect of temperature to give a measured value.

The components of the krill oil can be analyzed as described below.Unless otherwise specified, the analysis data shown in the presentspecification were obtained according to the procedures described above.

The phospholipids content can be measured by, for example, dissolving300 mg of krill oil in hexane, subjecting the resulting solution tosilica gel chromatography, eluting and collecting the adsorbed fractionsusing chloroform, vacuum distilling the solvent, and measuring theweight of the residue.

The fatty acids composition can be analyzed by methyl esterifyingconstituent fatty acids in the presence of boron trifluoride and thensubjecting them to gas chromatography. The fatty acids composition canbe determined by calculating the percentage that the peak area derivedfrom each of the constituent fatty acids accounts for in the total peakarea derived from the total fatty acids. The conditions for gaschromatographic analysis can be designed as described below.

Analyzer: 6890N Network GC System (Agilent Technologies);

Column: DB-WAX (column length: 30 m, internal diameter: 250 μm,thickness: 0.27 μm, model No.: 122-7032, J&W Scientific);

Column temperature: Raised from 180° C. to 230° C. at a rate of 30°C./min and then hold at 230° C. for 15 minutes;

Inlet temperature: 250° C.;

Detector temperature: 250° C.;

Detector: FID;

Carrier gas: Helium.

The astaxanthin content was measured according to the method disclosedby Jacobs P. B., et al. (Comp. Biochem. Physiol., 72B, 157-160, 1981).Free astaxanthin was prepared from an esterified product by an esteraseenzyme, and the total astaxanthin amount was quantified by HPLC on thebasis of the authentic sample.

The alcoholic injury mitigating agent and alcohol metabolism promotingagent of the present invention may optionally contain known componentssuch as coloring agents, preservatives, flavors, flavoring agents,coating agents, antioxidants, vitamins, amino acids, peptides, proteins,and minerals (e.g., iron, zinc, magnesium, iodine).

Examples of antioxidants includes dried yeast, glutathione, lipoic acid,quercetin, catechins, coenzyme Q10, enzogenol, proanthocyanidins,anthocyanidin, anthocyanin, carotenes, lycopene, flavonoid, resveratrol,isoflavones, zinc, melatonin, ginkgo biloba leaf, Alpinia zerumbet leaf,hibiscus, or extracts thereof.

Examples of vitamins include vitamin A group (for example, retinal,retinol, retinoic acid, carotene, dehydroretinal, lycopene, and saltsthereof), vitamin B group (for example, thiamine, thiamine disulfide,dicethiamine, octothiamine, cycotiamine, bisibuthiamine, bisbentiamine,prosultiamine, benfotiamine, fursultiamine, riboflavin, flavin adeninedinucleotide, pyridoxine, pyridoxal, hydroxocobalamin, cyanocobalamin,methylcobalamin, deoxyadenosylcobalamin, folic acid, tetrahydrofolicacid, dihydrofolic acid, nicotinic acid, nicotinic acid amide, nicotinicalcohol, pantothenic acid, panthenol, biotin, choline, inositol,pangamic acid, and salts thereof), vitamin C group (ascorbic acid andderivatives thereof, erythorbic acid and derivatives thereof, andpharmacologically acceptable salts thereof), vitamin D group (forexample, ergocalciferol, cholecalciferol, hydroxycholecalciferol,dihydroxycholecalciferol, dihydrotachysterol, and pharmacologicallyacceptable salts thereof), vitamin E group (for example, tocopherol andderivatives thereof, ubiquinone derivatives and pharmacologicallyacceptable salts thereof), and other vitamins (for example, carnitine,ferulic acid, γ-oryzanol, orotic acid, rutin (vitamin P), eriocitrin,hesperidin, and pharmacologically acceptable salts thereof).

Examples of amino acids include leucine, isoleucine, valine, methionine,threonine, alanine, phenylalanine, tryptophan, lysine, glycine,asparagine, aspartic acid, serine, glutamine, glutamic acid, proline,tyrosine, cysteine, histidine, ornithine, hydroxyproline, hydroxylysine,glycylglycine, aminoethylsulfonic acid (taurine), cystine, orpharmacologically acceptable salts thereof.

The alcoholic injury mitigating agent and alcohol metabolism promotingagent of the present invention may be prepared in a suitable form forpharmaceutical compositions, functional foods, health foods,supplements, and others, for example, in the form of various solidpharmaceutical drugs such as granules (including dry syrups), capsules(soft capsules, hard capsules), tablets (including chewable tablets),powders, or pills, or liquid pharmaceutical drugs such as liquid drugsfor internal use (including liquids, suspensions, syrups).

Additives to be used for producing a pharmaceutical preparation include,but are not limited to, vehicles, lubricants, binders, disintegrators,plasticizers, dispersants, wetting agents, antiseptics, thickeningagents, pH adjustors, coloring agents, corrigents, surfactants, andsolubilizers. When preparing the inventive agent in the form of a liquiddrug, a thickening agent such as pectin, xanthan gum, or guar gum can beadded. The inventive agent can be made into a coated tablet using acoating agent or made into paste glue. The inventive agent can beprepared in any other forms according to conventional preparationmethods.

Further, the composition of the present invention can be added to anyfoods and beverages that can be mixed with fats and oils. For example,the inventive composition can be used as an additive for variousbeverages and foods such as confectioneries, bread, and soup. Thecomposition is preferably added to, for example, drinks that are lightand easy to drink before alcohol consumption, confectionaries such aschewable tablets, and snack foods to go with alcohol. The processes forproducing such foods and beverages are not particularly limited as longas the effects of the invention are impaired: in other words, they canbe produced according to any processes that are commonly used by thoseskilled in the art in respective applications. The inventive compositionmay be used in combination with components that are generally used toprevent drunkenness, such as fish and shellfish (e.g., Cyrenidae)extracts containing taurine or the like, or turmeric extracts containingcurcumin or the like. Alternatively, the composition can be used withtaurine or curcumin

EXAMPLES

The present invention will be specifically described by way of Examplesgiven below, but the scope of the present invention is not limitedthereto.

Example 1 Preparation of Krill Oil

The krill oil can be prepared by any procedures as typically disclosedin WO 2010/035749 A1 and WO 2010/035750 A1. The specific preparationexample is described below.

Fresh Antarctic krill (10 t) just after being caught was squeezed usinga meat separator (BAADER; Model: BAADER 605) to give a squeezed liquid(3 t). The resulting squeezed liquid (800 kg) was put in a stainlesstank and heated by applying steam at 140° C. directly to it. The heatingwas stopped after the temperature of the squeezed liquid was confirmedto reach 85° C. at the end of the heating for about 60 minutes. Thevalve on the bottom of the tank was opened to remove liquid componentsthat were able to pass through openings of 2 mm mesh by allowing them todrop under gravity, and the solids (heat-coagulated product) remainingon the mesh were washed by showering them with the same amount (3 t) ofwater. Then, the heat-coagulated product was put in aluminum trays at arate of 12 kg per tray and was flash-frozen in a contact freezer.

The resulting frozen heat-coagulated product (1 t) was put in water(3,000 L), heated with stirring to 65° C., and kept for 10 minutes.After being drained using a 24-msh nylon screen, the solids were putagain in water (3,000 L, 20° C.). After being stirred for 15 minutes,the suspension was drained using a 24-mesh nylon screen and treatedusing a centrifuge (Centrifugal Separator O-30 manufactured by TanabeWilltec Inc.) for 15 seconds to give the solids (564 kg, 73% moisture).Tocopherol (1.54 kg) was added to the resulting solids, and they weremixed well with a mixer and dried in hot air at 60° C. for 3.2 hours togive a dry product (148.4 kg).

Then, 99% (v/v) ethanol (1,200 L) was added to the resulting dry product(299.6 kg), and the mixture was heated to 60° C. and stirred for 2hours. After the stirring, the mixture was passed through a 100-meshnylon screen to separate it into the solid and liquid phases by allowingit to drop under gravity, whereby extract A and extraction sediments a)were obtained. 99% (v/v) ethanol (800 L) was added to extractedsediments a), and the mixture was heated to 60° C. and stirred for 2hours. After the stirring, the mixture was separated into the solid andliquid phases using a 100-mesh nylon screen to give extract B andextracted sediments b). 99% (v/v) ethanol (700 L) was added to extractedsediments b), and the mixture was heated to 60° C. and stirred for 2hours. After the stirring, the mixture was passed through a 100-meshnylon screen to separate it into the solid and liquid phases, wherebyextract C and extracted sediments c) (390 kg) (the weight was reduced to61.8% after drying at 105° C. for 4 hours) were obtained. Extracts A, B,and C were mixed into one (2,089 kg), and the mixture was concentratedunder reduced pressure at a liquid temperature of 60° C. or lower todistill off ethanol and water, whereby an extract (141.6 kg) wasyielded. The resulting extract was used as kill oil in the study thatfollows.

The results of the analysis of the krill oil for phospholipids content,astaxanthin content, and fatty acids composition are shown in Tables 1and 2.

TABLE 1 Component Unit Measured value Phospholipids (%) 47.2 Astaxanthin(ppm) 188

TABLE 2 Fatty acid composition Fatty acid (%) C14:0 10.9 C16:0 20.3C18:1 17.1 C18:2 1.6 C18:3 1.6 C18:4 2.8 20:5 (EPA) 15.0 22:6 (DHA) 7.3

Example 2 Administration of the Krill Oil to Test Animals

(1) Preparation of a Test Substance

The krill oil to be orally administered was prepared as described belowand stored in a brown glass bottle until use. The control group wasadministered only the same amount of olive oil.

Test substance for use to administer 200 mg of krill oil: Prepared bysuspending the krill oil in olive oil using a pestle and mortar suchthat 200 mg of the krill oil was contained in a 3 mL suspension.

Test substance for use to administer 1000 mg of krill oil: Prepared bysuspending the krill oil in olive oil using a pestle and mortar suchthat 1000 mg of the krill oil was contained in a 3 mL suspension.

(2) Preparation of a 60% (v/v) Ethanol Solution

The solution was prepared by mixing ethanol (purity 99.5%, Wako PureChemical Industries, Ltd.) and water for injection (OtsukaPharmaceutical Factory, Inc.) at a ratio of 60.3:39.7 and stored in abrown glass bottle at room temperature.

(3) Administration of the Test Substance and the 60% (v/v) EthanolSolution

The test substance and the 60% (v/v) ethanol solution were administeredto rats according to the schedule shown in FIG. 1. Unless otherwisespecified, the rats were bred under the following conditions:

Temperature: 20-26° C.;

Relative humidity: 40-70%;

Ventilation frequency: 10-20 times/hour;

Lighting time: 12 hours (7:00-19:00);

Feed: Voluntary intake of fish meal-free powdered feed (FR-1, FunabashiFarm Co. Ltd.);

Drinking water: Voluntary intake of tap water from a water bottle.

Eight-week-old male Wister rats were purchased (from Japan SLC, Inc.),and were quarantined and acclimated for 6 days. Those rats which wereobserved to have grown well and healthy in this period judging from thegeneral condition and body weight were selected and used as testanimals. The selected rats were divided into four groups (A1 to A4),each consisting of 12 rats, such that all groups had the same averagebody weight. The detailed information of the respective groups is shownin Table 3.

TABLE 3 Active administered 60% (v/v) ingredient liquid ethanol Testdose volume volume Number Group substance (mg/kg) (mL/kg) (mL/kg) ofrats A1 Untreated — — — 12 A2 Olive oil — 3 12 12 A3 Krill oil 200 3 1212 A4 Krill oil 1,000 3 12 12

The rats were fasted from one hour to 16 hours before receiving the 60%(v/v) ethanol solution. Then, they were forced to take the testsubstance orally once using a disposable oral feeding needle andsyringe. One hour after the administration of the test substance, the60% (v/v) ethanol solution was administered. The doses of the testsubstance and the 60% (v/v) ethanol solution were calculated on thebasis of the body weight of each animal measured on the day ofadministration.

Observation of general condition and blood sampling were made before and1, 2, 4, and 24 hours after the administration of the 60% (v/v) ethanolsolution.

(4) Measurement of Blood Ethanol Concentration

Heparin was added to the blood samples drawn before and 1, 2, and 24hours after the administration of the 60% (v/v) ethanol solution, thesamples were measured for blood ethanol concentration, and the averagevalue of this parameter was calculated for each group (FIG. 2).

All the test groups except the untreated group (A1) showed an increasein blood ethanol concentration after the administration of the 60% (v/v)ethanol solution, but the increase in blood ethanol concentration wassmaller in the krill oil-treated groups (A3 and A4) than in the oliveoil-treated group (A2). This effect was more prominent 24 hours afterthe administration of the ethanol solution. The results demonstrate thatconsumption of the krill oil promotes alcohol metabolism in adose-dependent manner.

(5) Observation of the General Condition of the Rats

The rats were observed for general condition before and 1, 2, 4, and 24hours after the administration of the ethanol solution (FIG. 3). Fromone hour after the ethanol administration, all the test groups exceptthe untreated group (A1) which received no 60% (v/v) ethanol solution(A2 to A4) were observed to be drunk due to the ethanoladministration—more specifically, slightly drunk, inebriated, somnolent,dead drunk, or comatose. Among them, the krill oil (1,000 mg/kg)-treatedgroup (A4) experienced significantly suppressed drunkenness as comparedwith the olive oil-treated group, and this effect was more prominent 24hours after the administration of the 60% (v/v) ethanol solution.

From 4 to 24 hours after the administration of the 60% (v/v) ethanolsolution, 2 rats each in the olive oil-treated group (A2) and the krilloil (200 mg/kg)-treated group (A3) died, possibly due to acutealcoholism caused by consumption of large amounts of alcohol. Incontrast, no rat in the krill oil (1,000 mg/kg)-treated group (A4) diedafter the ethanol administration.

(6) Measurement of Hematocrit (HCT)

EDTA-2K was added to the blood samples drawn before and 4 and 24 hoursafter the administration of the 60% (v/v) ethanol solution, and thesamples were used for HCT measurement (FIG. 4).

The olive oil-treated group (A2) showed an increase in HCT as comparedwith the untreated group (A1). The krill oil (200 mg/kg)-treated group(A3) displayed no significant difference in HCT compared with the oliveoil-treated group (A2) at the time of 4 hours after the ethanoladministration but showed a significant decrease in HCT at the time of24 hours after the ethanol administration. The increase in HCT was moreremarkably suppressed in the krill oil (1,000 mg/kg)-treated group (A4).The results demonstrate that the krill oil suppresses dehydration in adose-dependent manner.

(7) Measurement of Blood Aspartate Aminotransferase (AST) Activity

Heparin was added to the blood samples drawn before and 24 hours afterthe administration of the 60% (v/v) ethanol solution, and the sampleswere centrifuged at 1700×g at 4° C. for 15 minutes to obtain plasmasamples. The resulting plasma samples were used for AST activitymeasurement (FIG. 5).

All the groups (A2 to A4) which received the 60% (v/v) ethanol solutionshowed an increase in AST activity. The AST activity after the ethanoladministration was more suppressed in the krill oil-treated groups (A3and A4) than in the olive oil-treated group (A2). In particular, thisactivity was remarkably suppressed by the administration of 1,000 mg/kgof the krill oil (A4).

(8) Measurement of Blood Alanine Aminotransferase (ALT) Activity

Heparin was added to the blood samples drawn before and 24 hours afterthe administration of the 60% (v/v) ethanol solution, and the sampleswere centrifuged at 1700×g at 4° C. for 15 minutes to obtain plasmasamples. The resulting plasma samples were used for ALT activitymeasurement (FIG. 6).

All the groups (A2 to A4) which received the 60% (v/v) ethanol solutionshowed an increase in ALT activity. The ALT activity after the ethanoladministration was more suppressed in the krill oil-treated groups (A3and A4) than in the olive oil-treated group (A2). In particular, thisactivity was remarkably suppressed by the administration of 1,000 mg/kgof the krill oil (A4).

(9) Measurement of Blood Glucose Level

Heparin was added to the blood samples drawn before and 24 hours afterthe administration of the 60% (v/v) ethanol solution, and the sampleswere centrifuged at 1700×g at 4° C. for 15 minutes to obtain plasmasamples. The resulting plasma samples were used for measuring glucoselevel (FIG. 7).

After the administration of the 60% (v/v) ethanol solution, all thetreated groups (A2 to A4) showed an increase in blood glucose level. Ascompared with the untreated group (A1), the olive oil-treated group (A2)had a higher blood glucose level even 24 hours after the administrationof the ethanol solution. In the krill oil-treated groups (A3 and A4),the increase in blood glucose level was suppressed in a dose-dependentmanner.

Example 3 Effects of the Krill Oil on Alcohol Consumption in Humans

The effects of the krill oil on alcohol consumption in humans werestudied by measuring their breath ethanol concentration and breathacetaldehyde concentration after alcohol consumption.

(1) Preparation of Test Foods

Soft capsules each containing the krill oil prepared in Example 1 orrefined olive oil in an amount of 250 mg were prepared. Both types ofsoft capsules used were colored so that their content could not bedistinguished by their appearance.

(2) Subjects

Five healthy male subjects aged 40 or older.

(3) Test Method

A double blind crossover study using olive oil as the control wascarried out. A 2-week washout period was scheduled.

The subjects were prohibited from drinking alcohol since the day beforethe study, and were instructed to have a lunch of the uniform menu(boxed lunch with fried chicken) between 12:00 and 13:00 on the day ofthe study. After the lunch, they were prohibited from having anythingbut water. The study began at 16:00.

Thirty minutes before alcohol consumption, the subjects were instructedto taken 8 soft capsules containing the krill oil or olive oil (2 g ofthe krill oil or olive oil, at a dose of 23-34 mg per kg body weight ofthe subject). They consumed alcohol by drinking barley shochu with analcohol content of 25%. The alcohol intake was adjusted based on thebody weight of each subject so as to give a net alcohol intake of 0.5 gper kg body weight. The subjects were instructed to consume the adjusteddose of barley shochu over 10 minutes. After the beginning of thedrinking, they were only allowed to drink enough water to quench theirthirst.

They underwent sampling of breath 30, 60, 90, 120 and 150 minutes afterthe drinking. Expired air was sampled by inhaling air from their nose,holding their breath for 10 seconds, and then breathing into a zip-upplastic bag (280×200×0.04 mm) so as to fill it with their breaths. Thebreath samples were subjected to the measurement of ethanolconcentration using a detector (Gastec Corporation, GV-100S) and anethanol detector tube (Gastec Corporation, No. 92L) connected thereto,and also to the measurement of acetaldehyde concentration using adetector (Gastec Corporation, GV-100S) and an acetaldehyde detector tube(Gastec Corporation, No. 92L) connected thereto.

(4) Results

Ethanol was detected in all of the breath samples collected from thesubjects (5 persons). FIG. 8 shows the changes with time in ethanolconcentration in the breath samples. The ethanol concentrations shown inthis figure are expressed as the averages of the ethanol concentrationsin the breath samples from the subjects (5 persons). In the breathsamples collected 30 minutes after the alcohol consumption, the highestethanol concentration was detected but there was no significantdifference in ethanol concentration between the case where the subjectsreceived the krill oil and the case where they received olive oil.However, in the breath samples collected 60 minutes after the alcoholconsumption, a significant decrease in ethanol concentration wasobserved in the case where they received the krill oil as compared withthe case where they received olive oil (p=0.04, Wilcoxon signed ranktest).

Acetaldehyde was only detected in the breath sample collected from oneof the subjects (5 persons); the concentrations detected in the samplesfrom the other 4 subjects were below the limit of detection. FIG. 9shows the changes with time in acetaldehyde concentration in the breathsamples collected from that subject. The breath acetaldehydeconcentration was found to be remarkably lower in the case where hereceived the krill oil than in the case where he received olive oil.Also, in the case where he received the krill oil, the breathacetaldehyde concentration decreased to below the limit of detection atthe time of 120 minutes after the alcohol consumption.

The results presented above demonstrate that consumption of the krilloil promotes alcohol metabolism and suppresses an increase in theconcentration of acetaldehyde which is responsible for uncomfortablefeeling and organopathy such as alcoholic liver injury induced byalcohol consumption.

Example 4 Comparison with Soybean Lecithin and Refined Fish Oil

The breath acetaldehyde concentration was selected as an indicator thatwould show easily detectable differences, and the effects of soybeanlecithin and refined fish oil were confirmed in the subject who hadacetaldehyde detected in his breath in Example 3 for comparison.

(1) Preparation of Test Foods

The additional oils used were commercially available refined fish oil(28 wt. % EPA and 12 wt. % DHA of total fatty acids) and soybeanlecithin (60 wt. % phospholipids). Soft capsules each containing refinedfish oil or soybean lecithin in an amount of 250 mg were prepared as inExample 3.

(2) Subject

Fifty-year-old healthy male subject (weight 65 kg) in whose breathacetaldehyde was detected in Example 3.

(3) Test Method

Following the same procedure as in Example 3, soft capsules containingrefined fish oil and soybean lecithin were administered to the subject,breath samples were collected from him, and the samples were subjectedto the measurement of acetaldehyde concentration.

(4) Results

FIG. 10 shows the changes with time in breath acetaldehyde concentrationalong with the results obtained in FIG. 9. The breath acetaldehydeconcentration was found to be remarkably lower in the case where hereceived the krill oil than where he received olive oil, refined fishoil, or soybean lecithin.

Also, in the case where he received the krill oil, the breathacetaldehyde concentration decreased to below the limit of detection atthe time of 120 minutes after the alcohol consumption. However, in thecases where he received olive oil, refined fish oil, or soybeanlecithin, this concentration decreased to below the limit of detectionat the time of 150 minutes or later after the alcohol consumption.

The results presented above demonstrate that consumption of the krilloil promotes alcohol metabolism and suppresses an increase in theconcentration of acetaldehyde which is responsible for uncomfortablefeeling and organopathy such as alcoholic liver injury induced byalcohol consumption. The results also demonstrate that the effects ofthe krill oil are remarkably higher than those of refined fish oil,soybean lecithin, and the like.

The Examples given above demonstrate the following. Namely, the ratsadministered alcohol developed typical symptoms caused by alcoholconsumption such as change in apparent mobility (drunkenness),dehydration, increase in blood glucose level, increase in blood ALTactivity, and increase in blood AST activity. The krill oil, which iscapable of reducing the alcohol concentration in the body, reduced thesesymptoms and helped the rats to recover faster from the symptoms totheir normal state. These effects were also observed in humans, but nocomparable effect could not be produced by the consumption of eitherrefined fish oil which is a triglyceride containing EPA and DHA orsoybean lecithin comprising phospholipids as a major component. Thesefindings demonstrate that the effects of the present invention are basedon the characteristic effects of the krill oil which comprisesphospholipids containing EPA and DHA.

The invention claimed is:
 1. A method of suppressing alcoholic injury ina human after consumption of an alcoholic beverage comprisingadministering 1-20,000 mg of hill oil to the human in need of thesuppression of the alcoholic injury after consumption of the alcoholicbeverage; wherein the alcoholic injury is selected from the groupconsisting of an increase in blood ethanol concentration, a liver injurydue to alcohol, dehydration, and an increase in blood glucose level. 2.The method of claim 1, wherein the hill oil contains phospholipids in anamount of at least 25% by weight.
 3. The method of claim 1, wherein atleast 5% by weight of total fatty acids in the hill oil is ω3polyunsaturated fatty acids.
 4. The method of claim 1, wherein theproportion of ω3 polyunsaturated fatty acids in the total fatty acidspresent in the hill oil is 10-30% by weight.
 5. The method of claim 1,wherein at least 15% by weight of total fatty acids in the hill oil isω3 polyunsaturated fatty acids.
 6. The method of claim 1, wherein atleast 2% by weight of the total fatty acids in the krill oil iseicosapentaenoic acid.
 7. The method of claim 1, wherein at least 1% byweight of total fatty acids in the hill oil is docosahexaenoic acid. 8.The method of claim 1, wherein the hill oil contains astaxanthin in anamount of at least 100 ppm.
 9. The method of claim 1, wherein the hilloil is administered in an amount of 100-5000 mg.
 10. The method of claim1, wherein the hill oil is administered about 30 minutes beforeadministration of the alcoholic beverage.
 11. The method of claim 1,wherein the hill oil is administered after fasting for a period of 1hour to 16 hours.
 12. The method according to claim 1, wherein the krilloil is in the form of a composition selected from the group consistingof granules, dry syrup, soft capsule, hard capsule, tablet, chewabletablet, powder, pill, suspension, and liquid syrup.
 13. The methodaccording to claim 1, wherein the krill oil is in the form of acomposition comprising the hill oil and at least one additive selectedfrom the group consisting of lubricants, binders, disintegrators,plasticizers, dispersants, wetting agents, antiseptics, thickeningagents, pH adjustors, coloring agents, corrigents, surfactants, andsolubilizers.